Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
Primary Mediastinal Large B-Cell Lymphoma
About this trial
This is an interventional treatment trial for Primary Mediastinal Large B-Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Age >= 2 years
- Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma
- Children's Oncology Group (COG) Institutions: Use Karnofsky for patients >= 17 and < 18 years of age and Lansky for patients < 17 years of age
- Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
Pediatric Patients (age < 18 years): The following must have been obtained within 14 days prior to registration:
- Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2, or
Serum creatinine =< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows:
- Age : 2 to < 6 year; Maximum serum creatinine (mg/dL): 0.8 (male; 0.8 (female)
- Age : 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female)
- Age : 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
- Age : 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
- Age : >= 16 years to < 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
- Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome
- Age >= 18 years: Ejection fraction of >= 50% by echocardiogram
- Age < 18 years: Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Administration of prior anti-cancer therapy except as outlined below:
- A short course (=< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms
- A single course of COP (cyclophosphamide, vincristine, and prednisone)
- One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, or a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131) that has not started more than 21 days prior to enrollment
- Active ischemic heart disease or heart failure
- Active uncontrolled infection
- Central nervous system (CNS) involvement of lymphoma
- Previous cancer that required systemic chemotherapy and/or thoracic radiation. Other cancers will be permitted if in remission x 3 years
- Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment
- In patients < 18 years of age hepatitis B serologies consistent with past or current infections
- Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin > 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
- Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study participation
- Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- USA Health Strada Patient Care CenterRecruiting
- Providence Alaska Medical CenterRecruiting
- Banner Children's at DesertRecruiting
- Banner University Medical Center - TucsonRecruiting
- Arkansas Children's HospitalRecruiting
- City of Hope Comprehensive Cancer CenterRecruiting
- Loma Linda University Medical CenterRecruiting
- Miller Children's and Women's Hospital Long BeachRecruiting
- Children's Hospital Los AngelesRecruiting
- Mattel Children's Hospital UCLARecruiting
- Valley Children's HospitalRecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Lucile Packard Children's Hospital Stanford UniversityRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Rady Children's Hospital - San DiegoRecruiting
- Children's Hospital ColoradoRecruiting
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterRecruiting
- Connecticut Children's Medical CenterRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- MedStar Georgetown University HospitalRecruiting
- Children's National Medical CenterRecruiting
- Broward Health Medical CenterRecruiting
- Golisano Children's Hospital of Southwest FloridaRecruiting
- University of Florida Health Science Center - GainesvilleRecruiting
- Memorial Regional Hospital/Joe DiMaggio Children's HospitalRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Tampa General HospitalRecruiting
- Saint Joseph's Hospital/Children's Hospital-TampaRecruiting
- Emory Proton Therapy CenterRecruiting
- Emory University Hospital MidtownRecruiting
- Children's Healthcare of Atlanta - Egleston
- Emory University Hospital/Winship Cancer InstituteRecruiting
- Emory Saint Joseph's HospitalRecruiting
- Memorial Health University Medical CenterRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Rush - Copley Medical CenterRecruiting
- Lurie Children's Hospital-Chicago
- Northwestern UniversityRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Carle at The RiverfrontRecruiting
- Decatur Memorial HospitalRecruiting
- Northwestern Medicine Cancer Center Kishwaukee
- Carle Physician Group-EffinghamRecruiting
- Northwestern Medicine Cancer Center Delnor
- Northwestern Medicine Lake Forest HospitalRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Loyola University Medical CenterRecruiting
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park RidgeRecruiting
- Saint Jude Midwest AffiliateRecruiting
- Southern Illinois University School of Medicine
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer CenterRecruiting
- Northwestern Medicine Cancer Center WarrenvilleRecruiting
- Riley Hospital for ChildrenRecruiting
- Blank Children's HospitalRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Eastern Maine Medical Center
- Maine Children's Cancer ProgramRecruiting
- Greater Baltimore Medical CenterRecruiting
- Sinai Hospital of BaltimoreRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Tufts Medical CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- C S Mott Children's HospitalRecruiting
- Children's Hospital of MichiganRecruiting
- Michigan State University Clinical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Beaumont Children's Hospital-Royal OakRecruiting
- Minnesota Oncology - BurnsvilleRecruiting
- Mercy HospitalRecruiting
- Fairview Southdale HospitalRecruiting
- Unity Hospital
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- Abbott-Northwestern HospitalRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- United HospitalRecruiting
- University of Mississippi Medical CenterRecruiting
- Saint Luke's HospitalRecruiting
- Siteman Cancer Center at West County HospitalRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Washington University School of MedicineRecruiting
- Siteman Cancer Center-South CountyRecruiting
- Mercy Hospital Saint LouisRecruiting
- Siteman Cancer Center at Saint Peters HospitalRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Renown Regional Medical CenterRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Memorial Sloan Kettering Basking RidgeRecruiting
- Hackensack University Medical CenterRecruiting
- Memorial Sloan Kettering MonmouthRecruiting
- Memorial Sloan Kettering BergenRecruiting
- Morristown Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Rutgers Cancer Institute of New Jersey
- Saint Joseph's Regional Medical CenterRecruiting
- Albany Medical CenterRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Roswell Park Cancer InstituteRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- NYP/Weill Cornell Medical CenterRecruiting
- University of RochesterRecruiting
- Stony Brook University Medical CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- Memorial Sloan Kettering NassauRecruiting
- New York Medical CollegeRecruiting
- Mission HospitalRecruiting
- AdventHealth Infusion Center AshevilleRecruiting
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- East Carolina UniversityRecruiting
- AdventHealth HendersonvilleRecruiting
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Children's Hospital Medical Center of AkronRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- Dayton Physician LLC-Miami Valley Hospital NorthRecruiting
- Kettering Medical CenterRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Emanuel Children's HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- Lehigh Valley Hospital-Cedar Crest
- Geisinger Medical CenterRecruiting
- Penn State Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Saint Christopher's Hospital for ChildrenRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Prisma Health Richland HospitalRecruiting
- Saint Francis HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Saint Francis Cancer CenterRecruiting
- Prisma Health Cancer Institute - Eastside
- Sanford USD Medical Center - Sioux FallsRecruiting
- East Tennessee Childrens HospitalRecruiting
- Saint Jude Children's Research HospitalRecruiting
- The Children's Hospital at TriStar CentennialRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Texas Tech University Health Sciences Center-Amarillo
- Dell Children's Medical Center of Central TexasRecruiting
- Driscoll Children's HospitalRecruiting
- Medical City Dallas HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- El Paso Children's HospitalRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- Houston Methodist HospitalRecruiting
- M D Anderson Cancer CenterRecruiting
- Covenant Children's HospitalRecruiting
- UMC Cancer Center / UMC Health SystemRecruiting
- Children's Hospital of San AntonioRecruiting
- Methodist Children's Hospital of South TexasRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Primary Children's HospitalRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Fairfax HospitalRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Carilion Children'sRecruiting
- Valley Medical CenterRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- Madigan Army Medical CenterRecruiting
- West Virginia University Charleston DivisionRecruiting
- University of Wisconsin Carbone Cancer Center
- Marshfield Medical Center-MarshfieldRecruiting
- John Hunter Children's Hospital
- The Children's Hospital at Westmead
- Queensland Children's Hospital
- Perth Children's Hospital
- University of Alberta HospitalRecruiting
- CancerCare ManitobaRecruiting
- Janeway Child Health CentreRecruiting
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHCRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)Recruiting
- HIMA San Pablo Oncologic HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Active Comparator
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Arm A (DA-EPOCH-R)
Arm B (DA-EPOCH-R, nivolumab)
Arm C (R-CHOP)
Arm D (R-CHOP, nivolumab)
Arm E (R-CHOP, radiation therapy)
Arm F (R-CHOP, nivolumab, radiation therapy)
See Detailed Description
Patients receive treatment as in Arm A. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and LP for CSF collection during screening. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Patients receive prednisone or prednisolone PO QD on days 1-5 and rituximab IV or rituximab and hyaluronidase human SC over 5 minutes on day 1 or 5. Patients also receive cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 1-15 minutes or up to 60 minutes, and vincristine sulfate IV over 1 or up to 60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Patients receive treatment as in Arm C. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles (5 if the patient had 1 prior cycle of treatment) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Patients receive treatment as in Arm C. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.
Patients receive treatment as in Arm D. Within 6-8 weeks after completion of chemotherapy, patients undergo radiation therapy over 25 fractions. Patients undergo ECHO during screening and as clinically indicated and LP for CSF collection optionally during screening. Patients also undergo CT or PET/CT throughout the trial. Additionally, patients undergo bone marrow biopsy and aspiration optionally during screening and as clinically indicated on study. Patients undergo blood sample collection on study.